ABZYMES Submitted by, Jeeva Raj Joseph 1st sem The pathogenic role of DNA abzymes is not quite clear. However Applications 1. Catalytic antibodies (abzymes): From concept to application ABSTRACT The importance of generati ng antibodies to catalyse specific reactions was discussed . Abzymes are these same molecules but with the addition of catalytic activity, a property rarely Potential Clinical Applications Of Abzymes.
|Published (Last):||14 September 2009|
|PDF File Size:||16.48 Mb|
|ePub File Size:||17.51 Mb|
|Price:||Free* [*Free Regsitration Required]|
Antibodies or immunoglobulins are essential proteins for human immunological functioning.
Abzymes: An Introduction
Antibodies are expressed on the membrane of B cells, a type of white blood cell essential for the adaptive immune response. After B cells are activated, they can differentiate into plasma cells that produce the same antibody in large quantities and expel abyzmes through exocytosis.
Abzymes are these same molecules but with the addition of catalytic activity, a property rarely seen in antibodies naturally, and are currently seeing exciting development in various therapeutic fields. Enzymes catalyze reactions that would otherwise be too slow for a biological time scale, and do this by having the following roles:.
Antibodies are most likely to be able to replicate the first three roles, but not the last two. This partial catalytic activity is reflected in the catalytic rate of abzymes, which is significantly lower than their enzyme counterparts.
Enzymes catalyze reactions by stabilizing the high-energy transition state, thereby reducing the energy required and causing the energy barrier of the reaction to be lowered. The most successful way of producing abzymes to date is by raising antibodies against transition state analogs. It is thought that if they have a high affinity for these analogs, they could reduce the energy barrier of a reaction therefore acting as an enzyme.
The other, less mainstream approach is to use an idiotypic pathway to produce an abzyme. This means raising an antibody that is complementary to the active site of the enzyme you want to mimic, then raising a second antibody to the variable region of the first antibody. This figure illustrates two ways of producing abzymes. The chemical pathway A uses transition state analogs to produce catalytic antibodies.
The biological pathway B uses an enzyme that already catalyzes the same reaction as the starting point Padiolleau-Lefevre, A remarkable example of the transition state analog pathway was demonstrated by G. Wayne Zhou et al They were able to crystallize a catalytic antibody 17E8 that was raised to a norleucine phosphonate transition state analog, as part of a peptide hydrolysis reaction.
The antibody also has a lysine strategically placed to stabilize to stabilize oxyanion formation and a small pocket for hydrophobic for side chains Zhou Remarkably, when both structures of trypsin a serine protease that also catalyses a peptide hydrolysis reaction and 17E8 containing the analog are superimposed, the active residues are in the exact same position relative to the substrate and to each other Figure 2.
Astonishingly, the immune system has created in about a week that evolution has taken many millennia to perfect. This figure is the superinposition of 17E8 and trypsin completed to bovine pancreatic trypsin inhibit. Trypsin in pink and white with 17E8 in red and yellow Zhou, Antibodies have exceptional specificity and high affinity, so combining this with catalytic activity seems like a perfect combination.
As a large protein drug they would lack cell permeability, and therefore the focus has been on extracellular targets such as pathogens, toxins, hormones, cytokines and membrane proteins. A variety of abzyme drugs have been and are being developed and trialled. Abzymes have been developed to hydrolyze the superantigenic region of gp, the CD4 binding site of the HIV virus.
This would prevent it from infecting its target cells, thus making the virus inert.
applicafions Recent research in this area has yielded ETNF-6 mAb, a catalytic antibody produced for exactly this purpose Hifumi, Each antibody has two variable regions, a feature that could be exploited in the development of new cancer treatments.
Researchers are trying to develop antibodies where one variable region binds to a cancer associated antigen and the other has abzyme activity that actives a pro-drug Goswami, The problem with this approach is lies in the heterogeneity of cancers, meaning cancer cells in a single patient may express different antigens.
Like in the development of any new therapeutic tools, the advancement of abzymes has not been without caveats and limitations. However, it is important to remember that the progress qpplications this novel field is on-going and what has been yielded so far certainly seems promising; it does not seem far-fetched to predict that with their versatility, abzymes could be used to treat a plethora of different diseases in the future.
Bioorg Med Chem Lett Padiolleau-Lefevre S, Naya R. You are commenting using your WordPress. You are commenting using your Twitter account.
You are commenting using your Facebook account. Notify me of new comments via email. Notify me of new posts via email. Facebook Print Twitter LinkedIn.
Study Notes on Abzymes (With Diagram)
Leave a Reply Cancel reply Enter your comment here Fill in your details below or click an icon to log in: Email required Address never made public.